Retinal neuroprotection by growth factors: A mechanistic perspective

Abstract

For more than a decade it has been known that certain growth factors inhibit apoptosis in genetically determined and experimental models of inner and outer retinal degeneration. The molecular mechanisms underlying these protective effects and the signaling that supports the survival of photoreceptors and retinal ganglion cells in these models have recently come under more in depth investigation. This paper reviews our current understanding of the balance of pro- and antiapoptotic signals that determine cell fate in the retina and how the activation of key signal transduction pathways by specific classes of neurotrophins protects retinal neurons.

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

“…Treatment with BDNF alone (without a graft) had no effect on the response latency which suggests that BDNF acts synergistically with other 'factors' released by the transplanted tissue. This combined effect may result in some restoration of the disturbed neural circuitry of the degenerating host retina which is supported by data from other investigators demonstrating neuro-protective effects of BDNF (Chaum, 2003;Ikeda et al, 2003;Keegan et al, 2003;Lawrence et al, 2004;Nakazawa et al, 2002;Paskowitz et al, 2004).…”

“…These studies have also provided investigators with information to assist in optimizing therapeutic strategies aimed at preventing visual loss and or restoring lost vision. Therapeutic interventions in animal models, including growth factor treatment, gene therapy, retinal prosthetics and retinal cell transplantation, have been presumed to improve visual sensitivity Seiler, 2002, 2004;Chaum, 2003;Delyfer et al, 2004;Loewenstein et al, 2004;Lund et al, 2001) by delaying the progression of the disease and/or by rescuing the remaining host photoreceptors. Some studies of retinal sheet transplants have suggested that transplanted photoreceptors may also contribute directly to the visual restoration Seiler et al, 2005a).…”

“…Studies performed in normal and retinal degenerate rat models demonstrate that BDNF has a neuroprotective role (Chaum, 2003;Gauthier et al, 2005;Ikeda et al, 2003;Keegan et al, 2003;Lawrence et al, 2004;Nakazawa et al, 2002;Paskowitz et al, 2004). Therefore, the present investigation evaluates the possible role of BDNF in promoting the functional efficacy of the retinal neuroblastic sheets transplanted into the subretinal space of retinal degenerative rats.…”

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

“…Neurotrophic factors have the ability to modulate neuronal growth during development to maintain existing cells and to allow recovery of injured neuronal populations. 68 In the retina, Lavail et al 69 More recently, recombinant AAV-2/2 encoding fibroblast growth factor family members FGF-2, FGF-5 and FGF-18 have been evaluated using a transgenic rat model of retinitis pigmentosa, the S334ter-4 rat line that expresses a mutated rhodopsin gene. Despite the lack of significantly increased electroretinograms (ERGs), treated rats displayed a greater number of surviving photoreceptors following subretinal injection of these vectors, suggesting the ability of these factors to protect photoreceptors from apoptosis in this rat model of RP.…”

Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings

“…The hydrogels employed (i.e., poly(ethylene glycol)-poly(lactic acid) (PEGPLA)) are composed of polymer elements that have been shown to dramatically increase biocompatibility of implanted devices [18], potentially reducing scar formation at the implant site. Additionally, these hydrogels can be designed to release a variety of bioactive compounds including neurotrophins, which are biomolecules that can influence neuronal survival and neurite extension in the retina [19][20][21]. Neurotrophins should promote growth of neuronal extensions toward the array, and thus decrease electrode-target separation distance and therefore thresholds.…”